Epilepsy is one of the most common neurological disorders after stroke, and affects at least 50 million people worldwide. It is diagnosed in a person having recurrent unprovoked seizures. These occur when cortical neurons fire excessively, hypersynchronously, or both, leading to temporary disruption of normal brain function. This might affect, for example, the muscles, the senses, consciousness, or a combination thereof. A seizure can be focal (confined to one part of the brain) or generalized (spread widely throughout the brain and leading to a loss of consciousness).
Epilepsy may occur for a variety of reasons; some forms have been classified into epileptic syndromes, most of which begin in childhood. Epilepsy is considered refractory to treatment when two or three anticonvulsant drugs have failed to control it. About 60% of patients will achieve control of their epilepsy with the first drug they use, whereas about 30% do not achieve control with drugs. When drugs fail, other options include epilepsy surgery, vagus nerve stimulation and the ketogenic diet. The ketogenic diet is often administered as a tube feed.
The ketogenic diet is effective in half of the patients who try it, and very effective in one third of the patients. In 2008, a randomised controlled trial showed a clear benefit for treating refractory epilepsy in children with the ketogenic diet, see Lancet Neurology 76: 500-506 (2008). There is some evidence that adults with epilepsy may benefit from the diet, and that a less strict regime, such as a modified Atkins diet, is similarly effective. The ketogenic diet has also been proposed as a treatment for a number of neurological conditions other than epilepsy; including patients experiencing epileptic syndromes, seizures and myoclonic jerk, persons in need of improvement of brain function or of cognitive skills, in particular of memory, for example patients suffering from Alzheimer's Disease or patients which suffer from a tumor, amyotrophic lateral sclerosis (ALS), Parkinson's disease, stroke, brain trauma, diabetes and obesity.
The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet primarily used to treat difficult-to-control (refractory) epilepsy in children. The diet mimics aspects of starvation by forcing the body to burn fats rather than carbohydrates. Normally, the carbohydrates contained in food are converted into glucose, which is then transported around the body and is particularly important in fuelling brain function. However, if there is very little carbohydrate in the diet, the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass into the brain and replace glucose as an energy source. An elevated level of ketone bodies in the blood, a state known as ketosis, leads to a reduction in the frequency of epileptic seizures.
Ketogenic formulas suitable for tube feeding should not form lumps or contain particles that form sediment, since this increases the risk of obstructing the tubes or restricting the flow. Also phase separation should be prevented, since one of the phases may remain in the package or tubing during feeding, which results in administration of an unbalanced nutrition and incomplete nutrition when the complete unit dose is not finished.
Thickeners are widely used in the art to prevent sedimentation of insoluble ingredients. However the viscosity of tube feeds is limited to a narrow range, in order to allow a constant and sufficiently high flow rate through the tubing when the diameter of the tube is small and a conventional administration pump is used. Especially for infants the tube feed diameter is relatively small thereby restricting the viscosity of the nutritional composition. Formulas that contain a high amount of fat are specifically sensitive to instability caused by phase separation. Similar considerations apply when the product is used as sip feed and a straw is used for consuming the product.
Presently many high-lipid food formulas are powder compositions that are prepared just before the administration of the tube feed. Ketocal Infant™ powder is an example of such a product. This has the advantage that the liquid product to be consumed by the patients does not need to be heated. Heating the product (e.g. sterilization) often results in sediment formation and phase separation. These physical processes are often aggravated during storage or cooling of the formula. The powder products have the disadvantage that the product is not ready to use, which is not convenient to the patients or nurses, and potential errors can be made in the preparation of the formula. In addition the use in tube feeding is limited due to instability issues of the formula. The stability of such products varies between 30 and 180 minutes depending on the batch of finished product tested. This is generally not stable enough for use in tube feed.